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2002 Fiscal Year Final Research Report Summary

The risk assessment and clarification of endocrine disrupting chemicals in environment. Use of P450 for the biomonitoring and bioremediation of environmental pollution-

Research Project

Project/Area Number 11358009
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 環境影響評価(含放射線生物学)
Research InstitutionHokkaido University

Principal Investigator

FUJITA Shoichi  Hokkaido Univ. Grad. School of Vet. Sci., 大学院・獣医学研究科, 教授 (10143314)

Co-Investigator(Kenkyū-buntansha) HOSHI Hidenobu  Osaka Prefecture Univ. College of Agriculture, 農学部, 助手 (30301188)
ISHIZUKA Mayumi  Hokkaido Univ. Grad. School of Vet. Sci., 大学院・獣医学研究科, 助手 (50332474)
KAZUSAKA Akio  Hokkaido Univ. Grad. School of Vet. Sci., 大学院・獣医学研究科, 助教授 (00002113)
Project Period (FY) 1999 – 2002
Keywordsbiomarker / endocrine disrupting chemicals / CYP1A / Cytochrome P450 / wild life / steroid hormone / environmental pollution / dioxin
Research Abstract

The usefulness of P450 as a biomarker and an assessing tool for the impact of environmental endocrine disrupting chemicals on the wild animals was studied.
Chlorinated hydrocarbon (CHC) levels in the blubber of Larga seals and Ribbon seals collected from the coastal waters of Hokkaido, Japan were determined in order to assess the hormonal effects of CHC exposure. In these animals, CYP1A expression levels were coincided with CHC accumulation levels. We also tried to isolate P450 isoforms such as CYP1A and CYP3A subfamilies, which contributed to elimination of xenobiotic and to catabolism of steroid hormone in mammals. We detemined the sequences and enzymatic characters of CYP1A1, CYP1A2 and CYP3A forms.
We also investigated the CHC effects on xenobiotic metabolisms and hormonal homeostasis in fish. We collected male and female carps from Hikiji river, where raw sewage containing dioxins had been released into river water for seven and a half years. The expression levels of CYP1A subfamily were coincided with dioxin accumulation levels. In contrast, estrogen level and GSI (gonadal somatic index) value were reduced in female carps collected from dioxin-contaminated river.

  • Research Products

    (54 results)

All Other

All Publications (54 results)

  • [Publications] Sakamoto KQ, Nakai, K, Aoto T, Yokoyama A, Ushikoshi R, Hirose H, Ishizuka M, Kazusaka A, Fujita S.: "Cytochrome P450 induction and gonadal status alteration in common carp (Cyprinus carpio) associated with the discharge of dioxin contaminated effluent to the Hikiji River, Kanagawa Prefecture, Japan"Chemosphere. 51(6). 491-500 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakamoto KQ, Kunisue T, Watanabe M, Masuda Y, Iwata H, Tanabe S, Akahori F, Ishizuka M, Kazusaka A, Fujita S.: "Accumulation patterns of polychlorinated biphenyl congeners and organochlorine pesticides in Steller's sea eagles and white-tailed sea eagles, threatened species, in Hokkaido, Japan"Environ Toxicol Chem.. 21(4). 842-847 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tilley RE, Kemp GD, Teramitsu I, Hall AJ.: "Isolation of two cytochrome P450 cDNAs, CYP1A1 and CYP1A2, from harp seal (Phoca groenlandica) and grey seal (Halichoerus grypus)"Comp Biochem Physiol C Toxicol Pharmacol.. 132(2). 181-191 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chiba I, Sakakibara A, Iwata H, Ishizuka M, Tanabe S, Akahori F, Kazusaka A, Fujita S.: "Hepatic microsomal cytochrome p450s and chlorinated hydrocarbons in largha and ribbon seals from Hokkaido, Japan : differential response of seal species to Ah receptor agonist exposure"Environ toxicol Chem. 21(4). 794-806 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Teraoka H, Maruyama Y, Takehana K, Iwanaga T, Hiraga T, Fujita S, Ohta T.: "Ca(2+) signaling in porcine duodenal glands by muscarinic receptor activation"Am J Physiol Gastrointest Liver Physiol.. 280(4). 729-737 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maruyama Y, et al.: "Uptake of the dopaminergic neurotoxin, norsalsolonol, into PC12 cells via dopamine"Archives of toxicology. 75. 209-213 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujita S, et al.: "P450 in wild animals as biomarker of environmental impact"Biomarkers. 6. 13-25 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maruyama Y, et al.: "Norsalsolinol uptake into secretory vesicles via vesicular monoamine transporter and its secretion by membrane depolarization or purinoceptor stimulation in PC12 cells"J Vet Med Sci. 63. 493-497 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chiba I, et al.: "Negative correlation between plasma thyroid hormone levels and chlorinated hydrocarbon levels accumulated in seal from the coast of Hokkaido, Japan"Environmental Toxicology and Chemistry. 20. 1092-1097 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto H, Watanabe T, Mizuno H, Endo K, Fukushige J, Hosokawa T, Kazusaka a, Fujita S.: "The antioxidant effect of DL-alpha-lipoic acid on copper-induced acute hepatitis in Long-Evans Cinnamon(LEC) rats"Free Radic Res.. 34(1). 69-80 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maruyama Y, Teraoka H, Iwata H, Kazusaka A, Fujita S.: "Inhibitory effects of endogenous dopaminergic neurotoxin, norsalsolinol on dopamine secretion in PC12 rat pheochromocytoma cells"Neurochem Int.. 38(7). 567-572 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto H, Watanabe T, Mizuno H, Endo K, Hosokawa T, Kazusaka A, Gooneratne R, Fujita S.: "In vivo evidence for accelerated generation of hydroxyl radicals in liver of Long-Evans Cinnamon (LEC) rats with acute hepatitis"Free Radic Biol Med.. 30(5). 547-554 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoon S, Kazusaka A, Fujita S.: "FTIR spectroscopic and HPLC chromatographic studies of carbon tetrachloride induced acute hepatitis in rats : damage in liver phospholipid membrane"Biopolymers. 57(5). 267-271 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoon S, Maruyama Y, Kazusaka A, Fujita S.: "Accumulation of diacylglycerol induced by CCl4-derived radicals in rat liver membrane and its inhibition with radical trapping reagent--FT-IR spectroscopic and HPLC chromatographic observations"Jpn J Vet Res.. 47(3-4). 135-144 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoon S, Maruyama Y, Kazusaka A, Fujita S.: "Application of FT-IR and ESR spectroscopic techniques to the study of CCl4-induced peroxidation in rat liver microsomes"Jpn J Vet Res.. 47(3-4). 151-154 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoon S, Kazusaka A, Fujita S.: "Accumulation of diacylglycerol in the liver membrane of the Long-Evans Cinnamon (LEC) rat with hepatitis : FT-IR spectroscopic and HPLC detection"Cancer Lett.. 151(1). 19-24 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Teramitsu I, Yamamoto Y, Chiba I, Iwata H, Tanabe S, Fujise Y, Kazusaka A, Akahori F, Fujita S.: "Identification of novel cytochrome P450 1A genes from five marine mammal species"Aquat Toxicol.. 51(2). 145-153 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto H, Hirose K, Hayasaki Y, Masuda M, Kazusaka A, Fujita S.: "Mechanism of enhanced lipid peroxidation in the liver of Long-Evans cinnamon (LEC) rats"Arch Toxicol.. 73(8-9). 457-464 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kim, E.-Y., Goto, R., Iwata, H., Masuda, Y., Tanabe, S., Fujita, S.: "Preliminary survey of lead poisoning of steller's sea eagle (Hliaeetus Pelagicus) and White-tailed sea eagle (Haliaeetus albicilla) in Hokkaido, Japan"Environmental Toxicology and Chemistry. 18,No.3. 448-451 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi J, Furuhata Y, Ikeda A, Takahashi M, Iwata H, Kazusaka A, Fujita S.: "Characterization of hepatic cytochrome P450 isozyme composition in the transgenic rat expressing low level human growth hormone"Xenobiotica. 29(12). 1203-1212 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Khlood EB, Miyoshi H, Iwata H, Kazusaka A, Kon Y, Hadid AH, Moustafe EK, Ghonim MH, Fujita S.: "Effects of concurrent exposure to 3 -methylcholanthrene and vitamin A on fetal development in rats"Jpn J Vet Res.. 7(1-2). 13-23 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimamoto, Y., Kitamura, H., Iwai, M., Saito, M., Kazusaka, A., Fujita, S.: "Mechanism of decrease in levels of hepatic P450 isozymes induced by intracerebral endotoxin : independence from sympathetic nervous and adrenocortical systems"Arch.Toxicol.. 73. 41-49 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimamoto Y, Tasaki T, Kitamura H, Hirose K, Kazusaka A, Fujita S.: "Decrease in hepatic CYP2C11 mRNA and increase in heme oxygenase activity after intracerebroventricular injection of bacterial endotoxin"J Vet Med Sci.. 61(6). 609-613 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura, A., Hirota, T., Morino, A., Imaoka, S., Funae, Y., Ymamoto, Y., Tasaki, T., Masuda, M., Kazusaka, A., Fujita, S.: "Cytochrome P450 isoforms responsible for the N-deethylation and cyclohexane-hydroxylation of NS-21"Xenobiotica. 29(3). 243-252 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 石塚真由美, 藤田正一: "化学物質による野生生物及び生態系への影響とは-北海道の野生生物を中心に-"化学物質と環境. 58. 7-9 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐治尚介, 坂本健太郎, 石塚真由美, 数坂昭夫, 藤田正一: "ウグイを用いた小樽、石狩、美国港周辺の環境汚染の評価"野生生物と交通. 2. 37-44 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 石塚真由美, 岩田久人, 藤田正一: "7章 環境毒性"トキシコロジー(日本トキシコロジー学会 教育委員会). 290-303 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishizuka M, Yamamoto Y, Takada A, Kazuska A, Fujita S.: "The loss of enzyme activities by a single amino acid substitution of a newly cloned rabbit CYP2D isozyme, CYP2D24. International congress series 1233"Elsvier. 545(121-126) (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 藤田正一 編集: "毒性学 -生体・環境・生態系-"朝倉書店. 300 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura, A., Hirota, T., Morino, A., Imaoka, S., Funae, Y., Yamamoto, Y., Tasaki, T., Masuda, M., Kazusaka, A., Fujita, S.: "Cytochrome P450 isoforms responsible for the N-deethylation and cyclohexane-hydroxylation of NS-21"Xenobiotica 29. No.3. 243-252 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimamoto Y, Tasaki T, Kitamura H, Hirose K, Kazusaka A, Fujita S.: "Decrease in hepatic CYP2C11 mRNA and increase in heme oxygenase activity after intracerebroventricular injection of bacterial endotoxin"J Vet Med Sci.. Jun;61(6). 609-613 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimamoto, Y., Kitamura, H., Iwai, M., Saito, M., Kazusaka, A., Fujita, S.: "Mechanism of decrease in levels of hepatic P450 isozymes induced by intracerebral endotoxin : independence from sympathetic nervous and adrenocortical systems"Arch. Toxicol.. 73. 41-49 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Khlood EB, Miyoshi H, Iwata H, Kazusaka A, Kon Y, Hadid AH, Moustafe EK, Ghonim MH, Fujita S.: "Effects of concurrent exposure to 3-methylcholanthrene and vitamin A on fetal development in rats"Jpn J Vet Res.. Aug;47(1-2). 13-23 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi J, Furuhata Y, Ikeda A, Takahashi M, Iwata H, Kazusaka A, Fujita S.: "Characterization of hepatic cytochrome P450 isozyme composition in the transgenic rat expressing low level human growth hormone"Xenobiotica. Dec;29(12). 1203-1212 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kim, E.-Y., Goto, R., Iwata, H., Masuda, Y., Tanabe, S., Fujita, S.: "Preliminary survey of lead poisoning of steller's sea eagle (Haliaeetus Pelagicus) and White-tailed sea eagle (Haliaeetus albicilla) in Hokkaido, Japan"Environmental Toxicology and Chemistry 18. No.3. 448-451 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto H, Hirose K, Hayasaki Y, Masuda M, Kazusaka A, Fujita S.: "Mechanism of enhanced lipid peroxidation in the liver of Long-Evans cinnamon (LEC) rats"Arch Toxicol.. Nov;73(8-9). 457-464 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoon S, Kazusaka A, Fujita S.: "Accumulation of diacylglycerol in the liver membrane of the Long-Evans Cinnamon (LEC) rat with hepatitis : FT-IR spectroscopic and HPLC detection"Cancer Lett.. Apr 3;151(1). 19-24 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoon S, Maruyama Y, Kazusaka A, Fujita S.: "Application of FT-IR and ESR spectroscopic techniques to the study of CC14-induced peroxidation in rat liver microsomes"Jpn J Vet Res.. Feb;47(3-4). 151-154 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoon S, Maruyama Y, Kazusaka A, Fujita S.: "Accumulation of diacylglycerol induced by CC14-derived radicals in rat liver membrane and its inhibition with radical trapping reagent--FT-IR spectroscopic and HPLC chromatographic observations"Jpn J Vet Res.. Feb;47(3-4). 135-144 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maruyama Y, Teraoka H, Iwata H, Kazusaka A, Fujita S.: "Inhibitory effects of endogenous dopaminergic neurotoxin, norsalsolinol on dopamine secretion in PC12 rat pheochromocytoma cells"Neurochem Int.. Jun 1;38(7). 567-572 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maruyama Y, Suzuki Y, Kazusaka A, Fujita S.: "Norsalsolinol uptake into secretory vesicles via vesicular monoamine transporter and its secretion by membrane depolarization or purinoceptor stimulation in PC12 cells"J Vet Med Sci.. May;63(5). 493-497 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maruyama Y, Suzuki Y, Kazusaka A, Fujita S.: "Uptake of the dopaminergic neurotoxin, norsalsolonol, into PC12 cells via dopamine transpoter"Archives of toxicology. 75(4). 209-213 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto H, Watanabe T, Mizuno H, Endo K, Hosokawa T, Kazusaka A, Gooneratne R, Fujita S.: "In vivo evidence for accelerated generation of hydroxyl radicals in liver of Long-Evans Cinnamon (LEC) rats with acute hepatitis"Free Radic Biol Med.. Mar 1;30(5). 547-554 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Teraoka H, Maruyama Y, Takehana K, Iwanaga T, Hiraga T, Fujita S, Ohta T.: "Ca(2+) signaling in porcine duodenal glands by muscarinic receptor activation"Am J Physiol Gastrointest Liver Physiol.. 280(4). G729-G737 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Teramitsu I, Yamamoto Y, Chiba I, Iwata H, Tanabe S, Fujise Y, Kazusaka A, Akahori F, Fujita S.: "Identification of novel cytochrome P450 1A genes from five marine mammal species"Aquat Toxicol.. Dec 1;51(2). 145-153 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoon S, Kazusaka A, Fujita S.: "FTIR spectroscopic and HPLC chromatographic studies of carbon tetrachloride induced acute hepatitis in rats : damage in liver phospholipid membrane"Biopolymers. 57(5). 267-271 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujita S, Chiba I, Ishizuka M, Hoshi H, Iwata H, Sakakibara A, Tanabe S, Kazusaka A, Masuda M, Masuda Y, Nakagawa H.: "P450 in wild animals as biomarker of environmental impact"Biomarkers. 6(1). 13-25 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto H, Watanabe T, Mizuno H, Endo K, Fukushige J, Hosokawa T, Kazusaka A, Fujita S.: "The antioxidant effect of DL-alpha-lipoic acid on copper-induced acute hepatitis in Long-Evans Cinnamon (LEC) rats"Free Radic Res.. Jan;34(1). 69-80 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chiba I., Sakakibara A, Goto Y, Isono T, Yamamoto Y, Iwata H, Tanabe S, Shimazaki K, Akahori F, Kazusaka A, Fujita S.: "Negative correlation between plasma thyroid hormone levels and chlorinated hydrocarbon levels accumulated in seal from the coast of Hokkaido, Japan"Environ Toxicol Chem.. May;20(5). 1092-1097 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishizuka M, Yamamoto Y, Takada A, Kazusaka A, Fujita S.: "The loss of enzyme activities by a single amino acid substitution of a newly cloned rabbit CYP2D isozyme, CYP2D24"International congress series. 1233. 121-126 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tilley RE, Kemp GD, Teramitsu I, Hall AJ.: "Isolation of two cytochrome P450 cDNAs, CYP1A1 and CYP1A2, from harp seal (Phoca groenlandica) and grey seal (Halichoerus grypus)"Comp Biochem Physiol C Toxicol Pharmacol.. Jun;132(2). 181-191 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakamoto KQ, Kunisue T, Watanabe M, Masuda Y, Iwata H, Tanabe S, Akahori F, Ishizuka M, Kazusaka A, Fujita S.: "Accumulation patterns of polychlorinated biphenyl congeners and organochlorine pesticides in Steller's sea eagles and white-tailed sea eagles, threatened species, in Hokkaido, Japan"Environ Toxicol Chem.. Apr;21(4). 842-847 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chiba I, sakakibara A, Iwata H, Tanabe S, Kazusaka A, Fujita S.: "Hepatic microsomal cytochrome P450s and chlorinated hydrocarbons in largha and ribbon seals from Hokkaido, Japan : Differential response of seal species to Ah receptor agonist exposure"Environ Toxicol Chem.. 21(4). 794-806 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakamoto KQ, Nakai K, Aoto T, Yokoyama A, Ushikoshi R, Hirose H, Ishizuka M< Kazusaka A, Fujita S.: "Cytochrome P450 induction and gonadal status alteration in common carp (Cyprinus carpio) associated with the discharge of dioxin contaminated effluent to the Hikiji River, Kanagawa Prefecture, Japan"Chemosphere. May;51(6). 491-500 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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